Tobacco use is the leading cause of preventable death globally, claiming more than 7 million lives each year. The burden of disease is highest in low- and middle-income countries, where more than 80% of the world's 1.3 billion tobacco users reside. The World Health Organization (WHO) defines six proven strategies to reduce tobacco use, referred to by the acronym MPOWER, with one of the strategies being to offer tobacco users help with quitting. Many low- and middle-income countries provide tobacco-cessation services; however, only 31 meet the WHO best practice, defined as providing both cost-covered behavioral interventions and pharmacotherapy. In this article, case studies from India and Vietnam illustrate how cross-country differences in tobacco-related sociocultural norms, tobacco-use patterns (e.g., smokeless tobacco or water pipes), the tobacco-control regulatory environment, industry influence, and health care system financing shape treatment access and uptake. These cases further show that cost-effective population-level strategies, including quitlines, digital interventions, and systemwide screening for tobacco use paired with clinician advice to quit, are essential for expanding treatment reach. Combining these interventions with pharmacotherapy products that are included on the WHO Model List of Essential Medicines (e.g., cytisine and nicotine-replacement therapy) further improves cessation outcomes. System-level models, such as the Ask-Advise-Connect model (ask about tobacco use, advise to quit, connect to cessation help), offer a feasible, low-burden pathway for integrating cessation care into routine practice. Ultimately, curbing the rising global burden of tobacco-related disease requires establishing comprehensive cessation support as a universal standard of care, which would ensure equitable access for those most affected.

Syncope is a common clinical problem caused by transient cerebral hypoperfusion and encompasses reflex, orthostatic, and cardiac mechanisms. Accurate diagnosis relies on careful history taking and physical examination, as well as targeted testing guided by risk stratification. Management of syncope is determined on the basis of the underlying mechanism and focuses on reducing recurrence and injury risk. In older patients, syncope may manifest as unexplained falls. Early identification of high-risk features is critical to prevent adverse cardiovascular outcomes.

The development of effective treatment strategies for human immunodeficiency virus (HIV) infection is a major achievement. Antiretroviral drugs inhibit key steps in the viral replication cycle and consist of six mechanistic classes: HIV entry inhibitors, reverse-transcriptase inhibitors (both nucleosides and nonnucleosides), capsid inhibitors, integrase inhibitors, and protease inhibitors. Antiretroviral therapy (ART) suppresses viral replication, thereby enhancing immune function, decreasing morbidity and mortality, and preventing viral transmission. Consequently, ART is recommended for all persons with HIV infection. On the basis of randomized clinical trials, the Food and Drug Administration has approved 36 antiretroviral drugs for the treatment of HIV infection since 1987; of these, 28 are currently available in the United States, and combination ART regimens are used. Initial preferred ART regimens are potent, convenient, and unlikely to cause side effects and consist of an HIV integrase inhibitor with a high barrier to resistance combined with one or two nucleoside reverse-transcriptase inhibitors. In the majority of patients using current ART regimens, viral replication is durably suppressed below detectable levels. Patients receiving ART are monitored for virologic response over time, and if virologic failure occurs, the next regimen is selected on the basis of treatment history and the results of drug-resistance testing; often, antiretroviral drugs from new classes are administered. Today, the life expectancy of someone with HIV infection who consistently takes ART approaches that of the general population.

Fibromyalgia is characterized by widespread pain involving any body tissue and typically accompanied by fatigue and problems with sleep, mood, and memory. Fibromyalgia can occur alone or in combination with other chronic overlapping primary pain conditions, or it can be superimposed on other conditions, such as autoimmune disorders (secondary pain). In fibromyalgia, the central nervous system (CNS) is hyperresponsive to sensory stimuli generally. Successful pharmacologic and nonpharmacologic interventions focus on the CNS to support CNS quiescence and a return to homeostasis. Although fibromyalgia is rarely curable, most cases can be well managed in the context of primary care.

Andes virus (ANDV) is the sole orthohantavirus with documented human-to-human transmission. We summarize the epidemiology and clinical features of ANDV infection and review best practices in clinical management, as based on published expert consensus guidelines, field experience, and clinical trials. We also evaluate currently available and investigational treatments (including the use of antiviral agents), assess emerging monoclonal antibody therapies, and outline prospects for vaccine development. Finally, we discuss important infection prevention and control measures.

Platelet-activating antibodies against platelet factor 4 (PF4) cause highly prothrombotic disorders with reduced platelet counts. In heparin-induced thrombocytopenia (HIT), these antibodies bind PF4-heparin complexes, causing heparin-dependent platelet activation. Less common autoimmune and spontaneous HIT variants that are triggered by heparin and nonpharmacologic polyanions, respectively, have atypical clinical features and antibodies with additional heparin-independent platelet-activating properties. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) antibodies directly target PF4. Initially, VITT was linked to adenoviral vector-based coronavirus disease 2019 vaccines, but in rare cases, an immune thrombocytopenia and thrombosis disorder that is clinically nearly identical to VITT can be caused by infection resulting from natural exposure to viruses, especially adenovirus. In persons with the IGLV3-21*02/*03 gene, anti-adenovirus protein VII antibody specificity shifts to PF4 by way of a specific somatic hypermutation (K31E) that creates VITT antibodies. In VITT-like monoclonal gammopathy of thrombotic significance, monoclonal anti-PF4 antibodies cause chronic prothrombotic conditions. Accurate diagnosis relies on distinct assays for HIT and VITT antibodies. Beyond anticoagulation, inhibition of FcγIIa receptor-mediated platelet activation may be needed for anti-PF4 disorders with heparin-independent reactivity (e.g., high-dose immune globulin in acute disease manifestations and Bruton's tyrosine kinase inhibitors in chronic manifestations).

In the acute phase of critical illness, adults have severe catabolism, inflammation, muscle loss, and gut dysfunction, all of which shape nutritional requirements. Early enteral nutrition supports gut integrity and microbiome health, but trials have shown that early short-term parenteral nutrition is a safe alternative when enteral feeding is not possible. Large trials have shown that early full-dose energy delivery offers no benefit over restrictive dosing and may increase gastrointestinal and metabolic complications, findings that support a restrictive nutrition strategy, especially in patients who have circulatory shock or are at risk for refeeding syndrome. Similarly, large trials have shown no advantage of high-dose over standard-dose protein and suggest harm in patients with acute kidney injury. Because adverse events are common with enteral nutrition, safe nutrition delivery requires gradual advancement, strategies for prevention of refeeding syndrome, glycemic control, and avoidance of routine gastric residual volume monitoring. Patient heterogeneity underscores the need for precise, biomarker-guided, phase-specific nutrition to preserve lean muscle mass and improve recovery.

Multiple sclerosis is a chronic autoimmune disorder that affects the central nervous system, causing episodes of neurologic dysfunction and often gradual disease progression. The immune system primarily targets myelin, the protective covering of nerve fibers, leading to inflammation and damage, and secondary neurodegeneration is a major cause of long-term disability. Common symptoms include vision problems, sensory disturbances, muscle weakness, balance difficulties, and bladder dysfunction. Important advances in treatment have improved outcomes in patients with relapsing forms of multiple sclerosis, particularly through highly effective immune-modifying therapies such as CD20-targeting monoclonal antibodies. However, treatment options for progressive forms remain limited, which highlights the need for therapies that can prevent progression and promote myelin repair. Comprehensive symptom management and lifestyle support are also essential to maintaining quality of life and reducing disability.

Early introduction of peanut protein reduces allergy prevalence by approximately 80%, with efficacy diminishing as introduction is delayed. Appropriate prevention involves ingestion of approximately 2 g of peanut protein weekly for infants at low risk and 4 to 6 g weekly for infants at high risk. Population-level implementation that targets all infants achieves greater reduction in disease burden than approaches that target only high-risk groups, although disparities exist among some ethnic groups and groups with restricted access to care. Peanut immunotherapy initiated in younger children (1 to 3 years of age) shows superior efficacy and higher rates of clinical remission as compared with immunotherapy initiated in older children. The natural history of untreated peanut allergy follows a trajectory of increasing peanut-specific IgE levels and clinical reactivity over time, underscoring the importance of early intervention during this narrow developmental window.

Bundibugyo virus is a relatively rare orthoebolavirus that has caused only two previously recognized disease outbreaks but remains capable of producing severe epidemic disease with substantial mortality. The 2026 outbreak of Bundibugyo virus disease in the Democratic Republic of Congo has highlighted persistent challenges in the detection of filovirus disease outbreaks, as well as in diagnosis, clinical management, and the public health response, particularly in resource-limited settings. As with other filovirus infections, effective control of the Bundibugyo virus disease outbreak depends on rapid identification of cases, laboratory confirmation of infection, isolation of cases, contact tracing, infection-prevention measures, protection of health care workers, and community engagement. Although no licensed vaccines or approved therapeutics specific to Bundibugyo virus disease are currently available, advances in supportive care have improved outcomes during recent filovirus disease outbreaks. Experimental evidence from studies involving nonhuman primates, serologic investigations with human samples, and monoclonal antibody research suggests that vaccines and therapeutics developed against Ebola virus may provide cross-protective activity against Bundibugyo virus. These observations support prototype-pathogen approaches to preparedness while underscoring the need for continued development of pathogen-specific countermeasures. The current outbreak reinforces the principle that a successful response to filovirus disease requires integration of medical countermeasures, clinical care, surveillance, diagnostics, and coordinated multinational public health operations.

Modern risk-adapted management of thyroid cancer involves risk stratification as an active, dynamic process that begins with the detection of a thyroid nodule and continues throughout the clinical course of diagnosis, active surveillance or treatment, and follow-up. Rooted in clinicopathological staging, which can be further refined with the molecular risk characterization of the tumor, initial management plans are developed and modified over time on the basis of the natural history of the disease and the response to therapy. We present a clinical framework for therapeutic decision making that can be used to compare, contrast, and illustrate the relative risks, benefits, and patient preferences that are integral to the development of a personalized management plan. We examine examples of therapeutic decision making in active surveillance of low-risk papillary thyroid cancer, minimalist therapeutic management options for low- and intermediate-risk thyroid cancer, and systemic therapies for advanced thyroid cancer, showing how the therapeutic decision-making framework can be used to achieve informed consensus and management recommendations.

The global rise in anticoagulant use has increased the number of major bleeding events that warrant timely and effective pharmacologic reversal. Reversal strategies should be informed by the pharmacodynamic and pharmacokinetic features of the anticoagulant and antidote, regulatory indications, quality of evidence, patient-specific factors, and availability of treatment options. Protamine sulfate neutralizes unfractionated heparin, whereas no specific antidotes exist for low-molecular-weight heparins or fondaparinux. Four-factor prothrombin complex concentrates effectively reverse vitamin K antagonists. Idarucizumab specifically reverses dabigatran, although delayed dabigatran rebound can occur. Andexanet alfa targets direct oral factor Xa inhibitors, but uncertainties regarding the efficacy-safety balance, monitoring, rebound, perioperative use, and cost have prompted off-label use of four-factor prothrombin complex concentrates, for which stronger evidence is needed. Key challenges remain, including determination of appropriate dosing, standardization and validation of laboratory monitoring, mitigation of thrombotic risk, and development of guidelines for perioperative treatment. Emerging agents aim to broaden targets and improve safety. Building high-quality evidence remains essential to advancing global, patient-centered anticoagulant and hemostatic care.

Leishmaniases comprise clinically distinct diseases caused by the protozoan parasite leishmania, which is transmitted through the bite of infected sand flies. Cutaneous leishmaniasis is the most common form and manifests as a localized skin lesion. Mucosal leishmaniasis causes destructive nose, mouth, and throat lesions. Visceral leishmaniasis is a potentially life-threatening form that results from bloodborne dissemination of the parasites. The number of cases of cutaneous leishmaniasis is increasing, particularly in the Eastern Mediterranean region, and the prevalence of visceral leishmaniasis is decreasing globally. Laboratory diagnosis of the leishmaniases has shifted to the use of molecular methods to test tissue samples (e.g., skin or bone marrow), which can be used to identify infecting species. Treatment is challenged by limited drug choices. A recent advance is the use of combination therapies for visceral leishmaniasis. Two human leishmaniasis vaccines are undergoing preclinical testing or are ready for human testing.

Vaccine hesitancy exists along a spectrum; most parents with hesitancy are motivated to protect their children but are often concerned about safety. Routine childhood vaccines recommended by the American Academy of Pediatrics have substantially reduced the incidence of disease and maintain a strong safety record. Clinicians are the most trusted source of vaccine information, and clear, confident recommendations are closely linked to higher uptake. Presumptive communication approaches are more effective than open-ended approaches, especially when paired with respectful dialogue. Empathy-driven, patient-centered strategies, including motivational interviewing, help address concerns, counter misinformation, and build trust while preserving relationships that may encourage future vaccination decisions.

Inflammatory myopathies are a heterogeneous group of autoimmune diseases characterized by immune-mediated damage to skeletal muscle. They are classified into five major subtypes: inclusion-body myositis, immune-mediated necrotizing myopathies, antisynthetase syndrome, overlapping myositis, and dermatomyositis, each with distinct clinical features and outcomes. Inclusion-body myositis and immune-mediated necrotizing myopathies primarily affect muscle, with prognosis largely determined by functional impairment, whereas antisynthetase syndrome, overlapping myositis, and dermatomyositis are systemic diseases that can involve the skin, joints, and lungs and may be life-threatening. The majority of inflammatory myopathies are associated with myositis-specific autoantibodies, which inform diagnosis, subtype classification, and prognosis. Advances in understanding the distinct pathomechanisms underlying each subgroup now enable increasingly targeted therapeutic approaches.

Cerebral amyloid angiopathy is a major cause of hemorrhagic stroke, a frequent contributor to age-related cognitive impairment, and a key component in adverse responses to beta-amyloid (Aβ) immunotherapy. Defined by pathological deposition of Aβ in the small blood vessels of the brain, cerebral amyloid angiopathy is most often diagnosed on the basis of magnetic resonance imaging studies showing multiple hemorrhages or leptomeningeal blood products within or overlying the cerebral cortex. The disorder typically manifests as hemorrhagic stroke or as a contributing factor to cognitive decline and, less commonly, with transient focal neurologic symptoms or a cerebral inflammatory autoimmune syndrome. The high risk of recurrent hemorrhagic strokes associated with cerebral amyloid angiopathy poses a particular challenge in patients with indications for antithrombotic therapy and dictates a carefully individualized weighing of risks and benefits. Ongoing research is focused on tools to aid in risk prediction, early diagnostic markers, and identification of key pathogenic steps as targets for disease-modifying therapies.

Barrett's esophagus develops as a result of chronic acid and bile reflux and carries an increased risk of esophageal adenocarcinoma. Because it has no specific symptoms, many patients do not receive a diagnosis or they present with symptoms of gastroesophageal reflux disease and other related risk factors or complications. Diagnosis relies on endoscopic and histopathological findings, including a visible columnar-cell-lined segment measuring at least 1 cm long that contains intestinal metaplasia with goblet cells. Ongoing surveillance focuses on early detection of malignant progression, particularly high-grade dysplasia and early-stage cancer, which allows curative endoscopic treatment and avoids the adverse effects associated with chemotherapy or esophagectomy. Participation in clinical trials is encouraged to improve detection, risk stratification, and management strategies.

Spinal epidural abscess is an infection in the epidural space. Patients typically present with localized back or neck pain (or both) that is accompanied by fever or neurologic symptoms. Magnetic resonance imaging with contrast enhancement is the diagnostic test of choice. An accurate microbiologic diagnosis is important and can be made with blood cultures, with tissue and fluid cultures obtained by image-guided needle aspiration or biopsy, or at the time of surgery. Staphylococcus aureus is the most frequent pathogen, causing more than 50% of infections. All patients with spinal epidural abscess should be promptly evaluated by a spine surgeon and an infectious-disease specialist. Many patients with spinal epidural abscess undergo surgery, although antimicrobial therapy alone may be curative in carefully selected patients.

Thrombosis is a recognized complication of sex hormone therapy, which includes hormone replacement for deficiencies, contraceptive therapy, treatment of heavy menstrual bleeding, gender-affirming hormone therapy, suppression of ovulation, oncologic hormone therapy, and assisted reproduction. This review examines the effects of sex hormones on hemostasis and the vasculature and summarizes current evidence on thrombotic risk, including the effects of hormone formulation, thrombophilias, previous thrombosis, and common clinical factors. Practical guidance on the prevention and treatment of hormone-associated venous thromboembolism, as well as on perioperative care of patients receiving sex hormone therapy, is also provided.

Celiac disease, a common autoimmune condition affecting approximately 1% of the population, can develop with exposure to gluten at any age. Diagnosis involves serologic testing, especially for IgA antibodies against tissue transglutaminase, and may include tests to confirm the presence of endomysial antibodies or even duodenal biopsies, although the latter are becoming less necessary. The presence of genes encoding HLA-DQ2 or HLA-DQ8 is a prerequisite for the disease. A gluten-free diet is the mainstay of treatment, but some adults have nonresponsive celiac disease, which warrants closer monitoring because of an increased risk of malignant conditions. Celiac disease also frequently co-occurs with other autoimmune disorders, such as type 1 diabetes mellitus and autoimmune thyroid disease.